(a) Field of the Invention
The invention relates to novel 2-phenylindoles having in the 3-position a six-membered carbocyclic group substituted in the 4-position by one or two carboxyl groups, to the preparation thereof, and to the use of the compounds as complement inhibitors.
The term "complement" refers to a complex group of proteins in body fluids that, working together with antibodies and other factors, play an important role as mediators of immune allergic, immunochemical and/or immunopathological reactions. The complement system is essential to combatting the effects of invasion by foreign biological and chemical entities. On the other hand, in the presence of antibody-antigen complexes, the complement proteins are involved in a series of reactions which may lead to irreversible membrane damage in the host organism. Accordingly, substances which are complement inhibitors have been found to be useful in treatment of acute inflammatory events in diseases such as rheumatoid arthritis, lupus erythematosus and glomerulo-nephritis, as documented in Inflammation: Mechanisms and Control (Lepow, I. H.; Ward, P. A., Editors), Academic Press, New York, NY, 1972, p. 223; and Immunological Diseases, Vol. II (Tolmage, D. W.; Rose, B.; Vaughan, J. H.; Editors), Little, Brown & Co., Boston, 1965, p. 995.
(b) Information Disclosure Statement
A wide variety of chemical substances has been found to cause inhibition at one or more sites of action in the complement pathway; Patrick, R. A. & Johnson, R. E. in Annual Reports in Medicinal Chemistry, Vol. 15, Academic Press, New York, NY, 1980; Chapter 20, pp. 193-201. None of the compounds thus far reported to have this activity has a structure closely related to the compounds of the present invention.
Freter, K., J. Org. Chem., Vol. 40, 2525-29 (1975) discloses a series of 3-cycloalkenylindoles prepared by reacting an indole derivative unsubstituted in the 3-position with cyclohexanone or a substituted cyclohexanone. Two of the compounds disclosed are ##STR1## None of the compounds described by Freter has any disclosed utility.